The detection of circulating human papillomavirus-specific T cells is associated with improved survival of patients with deeply infiltrating tumors
The detection of circulating human papillomavirus-specific T cells is associated with improved survival of patients with deeply infiltrating tumors
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DOI：
10.1002/ijc.25361
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发表时间：
2011-01-15
影响因子：
6.4
通讯作者：
van der Burg, Sjoerd H.
中科院分区：
文献类型：
--
作者：
Heusinkveld, Moniek;Welters, Marij J. P.;van der Burg, Sjoerd H.
在一大批hpv诱导的宫颈癌（CxCa）患者中进行了hpv特异性免疫与hla类型和预后因素的详细分析。患者为hla型，hpv16 /18特异性T细胞免疫通过增殖试验和使用新分离的PBMC的细胞头阵列以及hpv特异性T细胞的表型分析来评估。分析结果与已知疾病相关hla类型（DR7, DR13, DR15/DQ06），肿瘤浸润深度和大小，淋巴结（LN）状态和无病生存有关。对119例hla型CxCa患者进行分析。与荷兰人群相比，表达HLA-DR13单倍型的患者代表性不足（p = 0.014），而HLA-DR7在HPV16+ CxCa患者中代表性过高（p = 0.006）。在94例可抽血的患者中，29例（31%）检测到对HPV16/18的增殖反应，这与hpv特异性CD4+CD25+（活化）T细胞（p = 0.03）和hpv特异性CD4+CD25+ foxp3阳性T细胞（p = 0.04）的数量增加有关。foxp3阳性和阴性的hpv特异性CD4+CD25+ T细胞存在显著相关（p = 0.01）。有趣的是，hpv特异性增殖的检测与浸润深度相关（p = 0.020），而与HLA类型、肿瘤大小和LN状态无关。此外，在深度浸润性肿瘤患者中，hpv特异性免疫的检测与无病生存率的提高相关（p = 0.04）。总之，hpv特异性增殖性T细胞反应，包括更高百分比的hpv特异性CD25+和CD25+ foxp3阳性CD4+T细胞，在深浸润的CxCa肿瘤患者中更常被检测到，并与生存率提高相关。
A detailed analyses of HPV-specific immunity was performed in a large group of patients with HPV-induced cervical cancer (CxCa) in relation to HLA-types and prognostic factors. Patients were HLA-typed and HPV16/18-specific T-cell immunity was assessed by proliferation assay and cytometric bead array using freshly isolated PBMC and by phenotypic analysis of HPV-specific T cells. The results were analyzed in relation to known disease-related HLA-types (DR7, DR13, DR15/DQ06), invasion-depth and size of tumor, lymph node (LN) status and disease free survival. In total 119 HLA-typed patients with CxCa were analyzed. Patients expressing the HLA-DR13 haplotype were underrepresented as compared to the Dutch population (p = 0.014), whereas HLA-DR7 was overrepresented in patients with HPV16+ CxCa (p = 0.006). In 29 of 94 patients (31%) from whom blood could be tested, a proliferative response to HPV16/18 was detected, which was associated with increased numbers of HPV-specific CD4+CD25+ (activated) T cells (p = 0.03) and HPV-specific CD4+CD25+FoxP3-positive T cells (p = 0.04). The presence of both FoxP3-positive and negative HPV-specific CD4+CD25+ T cells was significantly correlated (p = 0.01). Interestingly, the detection of HPV-specific proliferation was associated with invasion depth (p = 0.020) but not with HLA type, tumor size nor LN status. Moreover, the detection of HPV-specific immunity was associated with an improved disease free survival (p = 0.04) in patients with deeply infiltrating tumors. In conclusion, HPV-specific proliferative T-cell response, comprising higher percentages of HPV-specific CD25+ and CD25+FoxP3-positive CD4+T cells, are more frequently detected in patients with deep infiltrating CxCa tumors and associated with an improved survival.